# Connecting specialized metabolism to social cues in actinomycete bacteria

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $379,628

## Abstract

PROJECT SUMMARY/ABSTRACT
Natural products from bacteria continue to be the frontline defense in the struggle against
bacterial infections, and have also found wide use as antifungals, anthelminthics, anti-cancer
drugs, and immunosupressants. One group of bacteria, the actinomycetes, has historically been
the deepest source of clinically-useful natural products. Over the last decade, numerous reports
have demonstrated that natural product biosynthesis often occurs in the context of actinomycete
interactions. These include interactions between microbes of different species, and cell-cell
coordination within colonies of single actinomycetes. Together, these findings have solidified the
idea that induction of natural product biosynthesis is socially driven in these bacteria. Despite
the importance of this social aspect, how these interactions unfold at the molecular level and
how interactions may best be harnessed for natural products discovery remain open questions.
The goals of this study are to understand how inter- and intra- species interactions activate
natural product biosynthesis at the molecular and systems levels, and to build framework for
translating these insights into natural product discovery. First, this work will examine how the
model actinomycete Streptomyces coelicolor activates expression of genes for antibiotic
production in the presence of other actinomycetes. This activation requires an unusual and
poorly understood signal transduction mechanism found in actinomycetes that shares parallels
with eukaryotic systems that rely on G protein activation. Second, this work seeks a systems-
level understanding of spatially coordinated antibiotic production within individual S. coelicolor
colonies. Knowledge generated from this objective may be employed to someday manipulate
cell fates within actinomycete cultures to drive natural products discovery and production. Third,
this work leverages actinomycete interactions for the discovery of novel natural products. This
research serves as a testbed for putting our knowledge of actinomycete interactions into
practice, with an emphasis on discovery of compounds with unusual mechanisms of action. In
its entirety, this work will illuminate the social drivers of natural product biosynthesis, and in the
long term, provide a foundation for harnessing microbial social cues and genetic regulation to
maximize future natural products discovery efforts.

## Key facts

- **NIH application ID:** 10623771
- **Project number:** 2R35GM128849-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Matthew F Traxler
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $379,628
- **Award type:** 2
- **Project period:** 2018-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10623771

## Citation

> US National Institutes of Health, RePORTER application 10623771, Connecting specialized metabolism to social cues in actinomycete bacteria (2R35GM128849-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10623771. Licensed CC0.

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